Deep hypothermic circulatory arrest facilitates repair of complex congenital cardiac anomalies in infants. Susceptibility to ischemia of central nervous system tissue however, remains the major limitation to the technique. Investigations in this laboratory have determined that an obstructive lesion of the cerebral microcirculation (no reflow phenomenon) which increases in severity with increasing time of normo-thermic circulatory arrest is abated for up to two hours by deep hypothermia. However, the precise etiology of the no reflow lesion and its causal relationship to cerebral death has not yet been established. Evidence exists that occlusion of capillaries by aggregates (fibrin, RBC's, platelets) cannot account for the microcirculatory lesion. More recently, we have shown that the persistence of microcirculatory collapse related to high intracapillary surface tension relative to local reperfusion pressure (critical opening pressure) is not a primary determinant of the no reflow lesion. In order to determine the effect of hypothermia on intracellular pH, the kinetics of metabolic intermediates and intracellular and extracellular water concentration during anoxia, triple label radionuclide studies with 14C-DMO, 3H-water, and 36Cl have been begun. Using the model of the no reflow phenomenon, changes in internal pH, intracellular metabolic intermediates, and shifts in water concentration will be determined in areas of no reflow as compared to reperfused areas defined by carbon black infusion.